Evidence map›Paper›PMID 29126155›Full record

ArticleHuman molecular genetics2018

Isl1 mediates mesenchymal expansion in the developing external genitalia via regulation of Bmp4, Fgf10 and Wnt5a.

Saunders T Ching, Carlos R Infante, Wen Du, Amnon Sharir, Sungdae Park, Douglas B Menke, Ophir D Klein

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.7field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Saunders T ChingDepartment of Orofacial Sciences, University of California, San Francisco, CA 94143, USA.
Carlos R InfanteDepartment of Genetics, University of Georgia, GA 30602, USA.
Wen DuDepartment of Orofacial Sciences, University of California, San Francisco, CA 94143, USA.
Amnon SharirDepartment of Orofacial Sciences, University of California, San Francisco, CA 94143, USA.
Sungdae ParkDepartment of Genetics, University of Georgia, GA 30602, USA.
Douglas B MenkeDepartment of Genetics, University of Georgia, GA 30602, USA.
Ophir D KleinDepartment of Orofacial Sciences, University of California, San Francisco, CA 94143, USA.
University of California, San Francisco · USUniversity of Georgia · USUniversity of Arizona · US

Funding

Harnessing natural stem cell-based strategies for mammalian dental renewalR35DE026602 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KLEIN, OPHIR D · 2016 to 2023
$8.0M
Developmental context and the control of appendage cis-regulatory networksR01HD081034 · NICHD · UNIVERSITY OF GEORGIA · PI MENKE, DOUGLAS BAY · 2014 to 2018
$1.5M
The Role of RAS/MAPK Signaling in Alveolar Process DevelopmentF32DE023702 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHARIR, AMNON · 2013 to 2015
$161k
The role of Sprouty genes in development of mammalian external genitaliaR01DK095002 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KLEIN, OPHIR D · 2012 to 2012
$150k
NICHD NIH HHS R01 HD081034NIDCR NIH HHS F32 DE023702NIDCR NIH HHS R35 DE026602NIDDK NIH HHS R01 DK095002
6 · The paper itself

Abstract

Genital malformations are among the most common human birth defects, and both genetic and environmental factors can contribute to these malformations. Development of the external genitalia in mammals relies on complex signaling networks, and disruption of these signaling pathways can lead to genital defects. Islet-1 (ISL1), a member of the LIM/Homeobox family of transcription factors, has been identified as a major susceptibility gene for classic bladder exstrophy in humans, a common form of the bladder exstrophy-epispadias complex (BEEC), and is implicated in a role in urinary tract development. We report that deletion of Isl1 from the genital mesenchyme in mice led to hypoplasia of the genital tubercle and prepuce, with an ectopic urethral opening and epispadias-like phenotype. These mice also developed hydroureter and hydronephrosis. Identification of ISL1 transcriptional targets via ChIP-Seq and expression analyses revealed that Isl1 regulates several important signaling pathways during embryonic genital development, including the BMP, WNT, and FGF cascades. An essential function of Isl1 during development of the external genitalia is to induce Bmp4-mediated apoptosis in the genital mesenchyme. Together, these studies demonstrate that Isl1 plays a critical role during development of the external genitalia and forms the basis for a greater understanding of the molecular mechanisms underlying the pathogenesis of BEEC and urinary tract defects in humans.

Indexed as

AnimalsBladder ExstrophyBone Morphogenetic Protein 4Embryonic DevelopmentFemaleFibroblast Growth Factor 10Gene Expression Regulation, DevelopmentalGenitaliaLIM-Homeodomain ProteinsMaleMesodermMiceMice, KnockoutOrganogenesisSignal TransductionTranscription FactorsBmp4 protein, mouseBone Morphogenetic Protein 4Fgf10 protein, mouseFibroblast Growth Factor 10insulin gene enhancer binding protein Isl-1LIM-Homeodomain ProteinsTranscription FactorsWnt-5a ProteinWnt5a protein, mouse

Identifiers

PMID29126155
PMCPMC5886284
OpenAlexW2767582236

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.